Assessing mTOR Pathway Signaling by 5-OXO-ETE and Hydroxystearic Acid
Additional Funding Sources
This work was supported by the Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences under Grant Nos. P20GM103408 and P20GM109095, and the National Institute of Neurological Disorders and Stroke under Grant No. R15NS096702 of the National Institutes of Health. We also acknowledge support from The Biomolecular Research Center at Boise State University with funding from with funding from the National Science Foundation, Grant Nos. 0619793 and 0923535, the MJ Murdock Charitable Trust, and the Idaho State Board of Education
Abstract
Autophagy dysfunction is associated with a large number of human diseases that include Parkinson’s and Alzheimer’s disease. Autophagy is an essential cellular process for breaking down organelles and protein aggregates. To date, considerable efforts have been directed towards modulating autophagy for therapeutic benefit. However, these efforts have not yielded a single successful clinical treatment that harnesses autophagy. Consequently, we are focusing upon identifying lipid regulators of autophagy- a research area garnering little attention. We have discovered two novel modulators of autophagy through lipidomic analysis, 5-OXO-ETE and hydroxystearic acid. In order to better understand the molecular mechanism for their inhibition of autophagy, we are assessing mTOR signaling, a canonical autophagy-regulating pathway, following treatment with these two lipids. Our hope is that understanding how these lipids affect autophagic activity will lead to innovative treatments for human disease.
Assessing mTOR Pathway Signaling by 5-OXO-ETE and Hydroxystearic Acid
Autophagy dysfunction is associated with a large number of human diseases that include Parkinson’s and Alzheimer’s disease. Autophagy is an essential cellular process for breaking down organelles and protein aggregates. To date, considerable efforts have been directed towards modulating autophagy for therapeutic benefit. However, these efforts have not yielded a single successful clinical treatment that harnesses autophagy. Consequently, we are focusing upon identifying lipid regulators of autophagy- a research area garnering little attention. We have discovered two novel modulators of autophagy through lipidomic analysis, 5-OXO-ETE and hydroxystearic acid. In order to better understand the molecular mechanism for their inhibition of autophagy, we are assessing mTOR signaling, a canonical autophagy-regulating pathway, following treatment with these two lipids. Our hope is that understanding how these lipids affect autophagic activity will lead to innovative treatments for human disease.
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